This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Alzheimer's disease (AD) is a progressive, neurodegenerative disorder, characterized by an age[unreadable]dependent loss of memory and an impairment of multiple cognitive functions. The major pathological features of AD are extracellular amyloid beta (A[unreadable]) plaques and intracellular neurofibrillary tangles. Synaptic damage and mitochondrial oxidative damage have been reported as early events in AD. Recent A[unreadable] and mitochondrial studies suggest that mitochondrial targeted therapeutic interventions may be effective in delaying AD progression in elderly individuals and in treating AD patients. In a recent study of clinical trials of AD patients from Russia, Doody and colleagues found that Dimebon was safe, well tolerated, and significantly improved the clinical course of patients with mild-to-moderate AD. However, mitochondrial protective mechanisms of Dimebon are still unclear. In the present pilot grant application, we propose to study mitochondrial dynamics, mitochondrial trafficking, and neurite outgrowth in embryonic and adult primary neurons from AD transgenic mice and wild[unreadable]type mice treated and untreated with mitochondrial targeted antioxidant, Dimebon. We propose 2 Specific Aims. Using 'live[unreadable]cell imaging technology'and confocal microscopy, in Aim 1 we will investigate mitochondrial dynamics in embryonic and adult primary neurons from AD transgenic mice. Aim 2 will assess mitochondrial and neuroprotective effects of Dimebon. The outcome of this pilot application will provide new insights in understanding the neuroprotective effects of Dimebon in AD.